The studies in this proposal are designed to characterize the central and peripheral site(s) and mechanism(s) of action underlying the effects of acute and repeated cocaine treatment on cognitive functioning, as assessed through learning performance in rodents. Cocaine has powerful effects on learning processes, suggesting that cocaine can be a useful tool in investigating mechanisms of learning. The widespread abuse of cocaine in our society today further underscores the importance of studying the relation between learning and cocaine, since learning plays a significant role in maintaining cocaine abuse. These studies will investigate how cocaine modulates learning and search for common mechanisms that may underlie cocaine's role in learning and abuse. Understanding these mechanisms may suggest means for reducing cocaine abuse. Experiments are designed to assess the relative contributions of peripheral and central sites and mechanisms of action to cocaine's learning effects. These studies in rats will utilize both positively and negatively motivated conditioning tasks. Cocaine's effects on retention of these tasks will be studied by administering the drug immediately after the completion of training, and then testing the animals for task retention 24 hours later. This paradigm eliminates the potential confounding influence of performance variables on measures of learning, since the animals are trained and tested in a non-drugged state. Initial experiments will investigate central and peripheral sites implicated in the effects on retention of acute cocaine treatment. Subsequent studies will determine whether the central and peripheral sites of action implicated in the acute effects of cocaine treatment on learning also are involved in the changes in cocaine's effect on learning that may be produced by repeated cocaine treatment. The final set of studies will determine whether the information obtained concerning the site(s) and mechanism(s) of action of cocaine's acute and chronic effects on learning can be used to reverse or alter the long-term consequences of cocaine administration.